TUMOR PROMOTION BY TCDD IN SKIN OF HRS/J HAIRLESS MICE
TUMOR PROMOTION BY TCDD IN SKIN OF HRS/J HAIRLESS MICE
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DOI：
10.1038/300271a0
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发表时间：
1982-01-01
期刊：
影响因子：
64.8
通讯作者：
GLOVER, E
中科院分区：
文献类型：
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作者：
POLAND, A;PALEN, D;GLOVER, E
2，3，7，8-四氯二苯并对二恶英(TCDD)是一组环境毒物卤代芳香烃1-3的原型，它能引起一种典型的急性毒性和生化反应，并通过立体特异性和可逆性与可溶性蛋白受体2，4，5结合来产生这些效应。TCDD6-9(和其他几种卤代芳香烃)10-13长期给药使大鼠肝癌和其他组织肿瘤的发病率增加。然而，由于TCDD不是突变剂14，15，并且在活体16中与DNA没有明显的结合，因此有人认为该化合物不是完全的致癌物，而是作为肿瘤促进剂，增强了已经启动的细胞17，18中的肿瘤表达。在大鼠肝脏19的两阶段癌变模型中，TCDD已被证明是有效的肿瘤促进剂，但在经典的小鼠皮肤模型(使用CD-1和瑞士韦氏小鼠)20，21中被证明无效。我们最近发现，TCDD会导致携带无毛(Hr)隐性性状的小鼠的表皮增生和角化过度，以及皮脂腺的鳞状化生，但对该位点上的野生型或杂合子小鼠的皮肤没有影响。在这里，我们研究了TCDD促进HRS/J无毛(hr/hr)小鼠及其同源有毛(hr/+)小鼠皮肤肿瘤形成的能力。在应用起始剂量的致癌物后，反复皮肤应用TCDD在hr/hr小鼠中产生了乳头状瘤，但在hr/+小鼠中没有。在HRS/J无毛小鼠中，TCDD的促癌作用引起的皮肤乳头状瘤的发生率和多样性与经典的促癌药物12-O-十四酰佛波醇-13-乙酸酯相同，但剂量是L的100倍。
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) serves as the prototype for a group of environmental toxicants, the halogenated aromatic hydrocarbons1–3, which evoke a characteristic pattern of acute toxic and biochemical responses, and which produce these effects by stereospecific and reversible binding to a soluble protein receptor2,4,5. The chronic administration of TCDD6–9(and several other halogenated aromatic hydrocarbons)10–13to rats and mice has produced an increased incidence of hepatocellular carcinomas as well as tumours in other tissues. However, because TCDD is not a mutagen14,15and does not bind appreciably to DNAin vivo16, it has been suggested that this compound is not a complete carcinogen, but rather acts as a tumour promoter, enhancing neoplastic expression in already initiated cells17,18. TCDD has been shown to be a potent tumour promoter in a two-stage model of carcinogenesis in rat liver19, but has proven ineffective in the classical model in mouse skin (using CD-1 and Swiss-Webster mice)20,21. We have recently shown that TCDD produces epidermal hyperplasia and hyper-keratosis, and squamous metaplasia of the sebaceous glands in mice bearing the recessive trait,hairless(hr), but causes no changes in the skin of mice which are wild type or heterozygous at this locus22. Here we examine the capacity of TCDD to promote tumour formation in the skin of HRS/J hairless (hr/hr) mice and their congeneic, haired (hr/+) littermates. Following the application of an initiating dose of a carcinogen, repeated skin application of TCDD produced papillomas inhr/hrmice but nothr/+ mice. In HRS/J hairless mice, tumour promotion by TCDD elicits the same incidence and multiplicity of skin papillomas as does the classical tumour .promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA), but at l/100th the dose.